Benzopyrans as selective estrogen receptor β agonists (SERBAs).: Part 3:: Synthesis of cyclopentanone and cyclohexanone intermediates for C-ring modification

Benzopyrans are selective estrogen receptor (ER) beta agonists (SERBAs), which bind the ER subtypes alpha and beta in opposite orientations. Here we describe the syntheses of cyclopentanone and cyclohexanone intermediates for SAR studies of the Gring on the benzopyran scaffold. Modification of the C-ring disrupts binding to ER alpha, thus improving ERP selectivity up to 100-fold. X-ray cocrystal structures confirm previously observed binding modes. (c) 2007 Elsevier Ltd. All rights reserved.